Our basic goal is to understand the mechanism of activation of the membrane-bound leukocyte oxidase, the factors that control it and the defect(s) in certain individuals susceptible to infection. Now that we are confident that the enzyme activity in the podosomes represents the phagocytosis equals associated oxidase, we plan to characterize it as part of the membrane using SDS gel electrophoresis and kinetically to isolate it and reconstitute using detergents, salt and replacement of possible prosthetic groups. In addition, utilizing the information we have gained concerning factors which affect activation, we will attempt to activate the enzyme in podosomes prepared from resting cells. We plan to examine these factors in the granulocytes and podosomes of patients with chronic granulomatous disease to see if we can artificially activate a latent enzyme activity.